日本研究人員在最新一期美國《科學》雜志網絡版上發(fā)表論文說,如果X染色體上的一個基因異常發(fā)揮作用,,體細胞克隆小鼠的出生率就會降低,,而如果使這個基因不發(fā)揮作用,,則可大幅提高克隆小鼠出生率。
體細胞克隆即從個體的皮膚等體細胞中取出細胞核,,植入去除了細胞核的卵細胞,然后將生成的胚胎移植到代孕母親的子宮內,,最終誕生與提供體細胞的動物擁有同樣遺傳信息的克隆動物,。雖然人類1996年就培育出了第一只體細胞克隆的哺乳動物綿羊多利,但此后克隆動物的出生率一直非常低,。
日本理化研究所生物資源中心研究員小倉淳郎率領的研究小組,,在分析利用克隆技術培育出的小鼠胚胎的基因時,發(fā)現(xiàn)在性染色體之一的X染色體上,,基因“Xist”異常發(fā)揮作用,。“Xist”基因能夠抑制其他基因的功能。
研究人員使小鼠的“Xist”基因不再發(fā)揮作用,,然后再用它們的體細胞培育克隆胚胎,,結果克隆小鼠的出生率大幅提高,相當于以前水平的八九倍,。
研究人員說,,今后這項技術有望應用于畜產領域。(生物谷Bioon.com)
原文摘要:
Science DOI: 10.1126/science.1194174
Impeding Xist Expression from the Active X Chromosome Improves Mouse Somatic Cell Nuclear Transfer
Kimiko Inoue,1,2 Takashi Kohda,3 Michihiko Sugimoto,1 Takashi Sado,4 Narumi Ogonuki,1 Shogo Matoba,1 Hirosuke Shiura,1 Rieko Ikeda,1 Keiji Mochida,1 Takashi Fujii,5 Ken Sawai,5 Arie P. Otte,6 X. Cindy Tian,7 Xiangzhong Yang,7 Fumitoshi Ishino,3 Kuniya Abe,1,2 Atsuo Ogura1,2,8,*
Cloning mammals by somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed in normal global gene expression and resulted in about an 8- to 9-fold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically downregulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.
1 BioResource Center, RIKEN, Tsukuba, Japan.
2 Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Japan.
3 Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
4 Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
5 Faculty of Agriculture, Iwate University, Iwate, Japan.
6 Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands.
7 Center for Regenerative Biology and Department of Animal Science, University of Connecticut, Connecticut 06269, USA.
8 The Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.